title: Close relations between podocyte injuries and membranous proliferative glomerulonephritis in autoimmune murine models.
abstract: BACKGROUND
  Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed.
  
  
  METHODS
  The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa(+) and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation.
  
  
  RESULTS
  Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl.
  
  
  CONCLUSIONS
  MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN.
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka
authors.forename: Hayato
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D018995:Myosin Heavy Chains; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D017252:CD3 Complex; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C525088:Myh9 protein, mouse; C407223:NPHS2 protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C503968:Synpo protein, mouse; C113267:nephrin; C001643:podocalyxin; D017493:Leukocyte Common Antigens; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains